This phase I/II trial is studying the side effects and best dose of imatinib mesylate and to see how well it works in treating patients with a recurrent brain tumor that has not responded to previous surgery and radiation therapy. Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth.

PRIMARY OBJECTIVES:

I. To identify the maximum tolerated dose of imatinib (imatinib mesylate) in patients with recurrent oligodendroglioma and mixed oligoastrocytoma that are currently on enzyme inducing anticonvulsant therapy. (Study 1) II. To assess the efficacy of imatinib in patients with recurrent oligodendrogliomas and mixed oligoastrocytomas (with pathologic evidence of oligodendrogliomatous component) as measured by progression-free survival, response, and overall survival. (Study 2) III. To acquire pilot data on a patient group not traditionally eligible for recurrent oligodendroglioma and mixed oligoastrocytoma clinical trials (those having > 2 prior chemotherapy regimens or 2 prior chemotherapy regimens for recurrent/progressive disease). (Study 3) IV. To examine the toxicity and safety of imatinib in patients with recurrent oligodendrogliomas and mixed oligoastrocytomas (with pathologic evidence of oligodendrogliomatous component). (Studies 1, 2, and 3) V. To perform a preliminary correlative study of 1p/19q alterations, alpha platelet-derived growth factor receptor (PDFGR) gene amplification and levels of related downstream signaling elements in tumor tissue, with clinical study endpoints. (Studies 1, 2, and 3) VI. To perform a descriptive correlative analysis of steady state pharmacokinetic data regarding imatinib and active metabolites with the study endpoints. (Studies 1, 2, and 3)

OUTLINE: This is a phase I, dose-escalation study followed by a phase II and a pilot study.

Inclusion Criteria:

• Study 1 Arm C:

  • Currently on anticonvulsants which can induce cytochrome p450 (phenytoin, carbamazepine, barbiturates, primidone and if unsure contact study chair)
  • =< 2 prior chemotherapy regimens (with maximum of 1 prior chemotherapy regimen for recurrent disease)

• Study 2 Arms A and B:

  • On or off anticonvulsants
  • =< 2 prior chemotherapy regimens (with maximum of 1 prior chemotherapy regimen for recurrent disease)

• Study 3 Arms D and E:

  • On or off anticonvulsants
  • > 2 chemotherapy regimens or 2 prior chemotherapy regimens for progressive/recurrent disease

• All Arms:

• Histological confirmation of a grade 2-4 oligodendroglioma, or mixed oligoastrocytoma grade 2-4 containing oligodendrogliomatous component on central pathology review prior to study registration, and a diagnosis of recurrence; tissues from all available prior surgeries should be sent, in particular those from time of initial diagnosis

• Measurable or evaluable disease by magnetic resonance imaging (MRI) or computed tomography (CT) scan

• Fixed dose of corticosteroids (or no corticosteroids) for at least 1 week prior to the pre-study baseline scan

• Patients undergoing surgery for initial or progressive disease, must be at least 2 weeks from the date of surgery, must have recovered from the effects of their surgery, and must have unequivocal tumor growth on the pre-study baseline neuroimaging study as compared to the first post-operative scan, unless there is a separate lesion or residual disease compatible with tumor that is not within the surgical bed

• Unequivocal evidence of tumor progression by MRI or CT scan performed =< 21days prior to study registration

• Must have failed surgery/radiotherapy (RT) and Temozolomide or nitrosourea based therapy

• >= 12 weeks since the completion of RT

• Absolute neutrophil count (ANC) >= 1500/mm^3

• Platelets (PLT) >= 100,000/mm^3

• Hemoglobin (Hgb) >= 9 g/dL

• Total bilirubin =< 1.5 mg/dL

• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 3 x upper limit of normal (ULN)

• Creatinine =< 2.0 mg/dL

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2

• >= 6 weeks since the last day of nitrosourea-based chemotherapy prior to study entry

• >= 4 weeks from any investigational agents prior to study entry

• >= 4 weeks from other chemotherapy prior to study entry

• >= 2 weeks from vincristine and biologic non-cytotoxic agents, e.g., tamoxifen, thalidomide, cis-retinoic acid, interferon, etc, prior to study entry

• Patients or designated individual(s) with durable medical power of attorney for the patient must be able to provide informed, written consent, and complete any required study questionnaire(s) within the specifications of this study

Exclusion Criteria:

• All Arms
• Receiving warfarin or heparin
• Received prior stereotactic radiosurgery, interstitial brachytherapy, or interstitial chemotherapy including carmustine (BCNU) wafers unless there is a separate lesion on MRI, which is not part of the previous treatment field
• Active uncontrolled infection
• History of myocardial infarction =< 6 months or congestive heart failure (CHF) requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias; patients must have a New York Heart Association (NYHA) of class II or less; (NYHA class I: patients with no limitation of activities; they suffer no symptoms from ordinary activities; class II: patients with slight, mild limitation of activity; they are comfortable with rest or with mild exertion; class III: patients with marked limitation of activity; they are comfortable only at rest; class IV: patients who should be at complete rest, confined to bed or chair; any physical activity brings on discomfort and symptoms occur at rest)
• Other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the interpretation of potential drug-induced toxicities
• Women of child-bearing potential, pregnant or nursing; such patients must have a negative pregnancy test (b-HCG) =< 7 days prior to study registration
• Men or women of childbearing potential, not willing to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.); the efficacy of oral contraceptives may be decreased in patients who receive p450-inducing anticonvulsants; for these patients, use of a second mode of contraception is recommended; patients of childbearing potential must utilize effective contraception and avoid becoming pregnant or fathering a child for 6 months after completing study drug
• Other active malignancy, besides skin carcinomas (must not be melanoma)
• Concomitant serious immunocompromised status (other than that related to concomitant steroids); patients that are human immunodeficiency virus (HIV) positive are eligible, provided that there is no other reason for exclusion, based on the eligibility as outlined elsewhere in this section
• Significant intratumoral hemorrhage on baseline MRI or CT, or other history of significant intratumoral hemorrhage